Angiomotins (Amots) are a family of adaptor proteins that 1) coordinate signaling events during cellular and neural differentiation and proliferation and 2) bind lipids with specificity via their Amot coiled-coil homology (ACCH) domain leading to membrane deformation. Amots have been shown to have a critical role in endothelial and epithelial cell migration, invasion and tubule formation, and they are believed to regulate angiogenesis, which promotes tumor growth and metastasis. Amot over expression and mutations have been linked to neuroepithelial tumors, such as glioblastomas, brain hemangioendotheliomas, neurofibromatosis, and other brain tumors. The role of Amots in epithelial and endothelial cancer growth and metastasis have been linked to poor prognosis and unfavorable clinical outcomes. The ACCH domain gives the Amot family the ability to selectively bind monophosphorylated phosphatidylinositols (PIPs) and cholesterol, as well as to target specific transcription factors away from the nucleus. Understanding the structure-function relationship of the ACCH domain may provide pathways to modulate protein sorting and downstream signaling events inducing cellular differentiation, cancer cell proliferation, and cell migration. The goal of this project is to use small angle X-ray scattering (SAXS) and wide angle X-ray scattering (WAXS) data to generate a solution structure of the Amot80/130 and AmotL2 (Mascot) ACCH domains. Additionally, this structure will be compared against theoretical models to determine the statistical accuracy of the theoretical models. Furthermore, we hypothesize that generating these models will allow us to determine the structure of another analogue of A80/130, the Angiomotin-like 1 (JEAP) ACCH domain.

Structural characterization of the ACCH domain of angiomotin family members

251st National Meeting (2016)

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